The study uses a randomized controlled study design of pediatric neurologists and developmental pediatricians and front-line (primary care) pediatricians to determine if use of FirstStepDx PLUS and Next StepDx PLUS are associated with higher clinical quality, less variability in clinical practice, and lower costs from decreased resource utilization. The Clinical Performance and Value Vignettes (CPV) used in this study simulate a clinical encounter for individuals with an atypical phenotype and clinical presentation indicative of a possible genetic disorder. We will measure the difference in combined diagnostic and treatment CPV® domain score post-intervention versus baseline comparing intervention and control groups

The study is an interventional longitudinal study design of physician practice. 225 specialist and general pediatricians without previous exposure to FirstStepDx PLUS or NextStepDx PLUS will be selected from a nationally representative list of approximately 25,000 board-certified pediatricians and 5,000 specialists. These physicians will be randomized into one of three arms: to receive information regarding FirstStepDx PLUS ("Intervention A"), to receive information about FirstStepDx PLUS and NextStepDx PLUS ("Intervention B") for use in clinical practice, and controls not receiving any intervention. Specifically we will test the hypotheses:

1. Clinical practice, specifically decisions around treatment of individuals with disorders postnatal development including DD, ASD, and ID will vary widely among all physician types. This documentation of variation in practice will demonstrate the need for a new diagnostic service that FirstStepDx PLUS and NextStepDx PLUS would fulfill
2. FirstStepDx PLUS and NextStepDx PLUS will improve the quality and appropriateness of care and therapeutic plans, as measured by the number of physicians that correctly act on the results of the assay

A Physician Questionnaire will be administered to all physicians. This questionnaire will assess physician, patient and practice characteristics. Data gathered from this set of questions will become part of the baseline (pre-intervention) assessment and used for analysis. At the baseline assessment, Clinical Performance and Value (CPVs) Vignettes, a validated tool to measure physician performance and behavior will be used. CPV vignettes have been used to establish clinical utility in the molecular diagnostic space.

The CPV vignettes used in this study will simulate a clinical encounter for a patient with an atypical clinical presentation indicative of a possible genetic developmental disorder. Each physician will provide open-ended responses regarding clinical care. These responses are scored in five domains (taking a medical history, performing a physical examination, ordering appropriate tests, making a diagnosis and prescribing treatment against explicit evidence and criteria as determined by the literature and by expert physicians. Results are presented as percentage correct controlling for primacy effects using case within pair randomization. Each case will take approximately 15-20 minutes to complete. All case responses will be completed electronically online and confidential. No physician or practice names are used when reporting the results of the study.

The CPVs will be randomly assigned to physicians for each to complete 3 CPVs™ (one from each type). Each of the CPVs will be scored by physicians for changes in clinical practice including treatment changes, frequency of follow up, laboratory tests and imaging studies ordered - see for scoring sheet.

The objective of this study is to assess how FirstStepDx PLUS (and NextStepDx PLUS) testing affects the variability of clinical practice and resultant impact.

Primary Endpoint Differences in CPV diagnosis/treatment domain score post-intervention versus baseline for the intervention and control group physicians).

Secondary Endpoints

• Difference in utilization of appropriate treatment including indicated versus unnecessary therapy pre- and post-intervention between intervention and control groups
• Difference in utilization of laboratory testing such as fluorescence in situ hybridization (FISH) analyses, global assessment, and utilization of other laboratory tests pre- and post-intervention, between intervention and control groups
• Difference in overall Clinical Performance and Value Vignettes (CPV®) scores post-intervention versus baseline between intervention and control groups

Inclusion Criteria:

1. Provide consent to participate in the study

2. Currently practicing board-certified physician in the following specialty areas:

   1. Pediatric neurologists
   2. Developmental pediatricians
   3. General pediatricians

3. Have practiced as a board-certified physician for greater than 2 but less than 30 years.

4. English-speaking

5. Community / non-academic based practice setting

6. ≥30 pediatric patients under care annually

7. Access to the internet

Exclusion Criteria:

1. Not board certified in their respective area of care
2. Academic-based practice
3. Have previously used FirstStepDx PLUS and/or NextStepDx PLUS in their care delivery
4. Have practiced as a board-certified physician for less than 2 or greater than 30 years.
5. Follow <30 pediatric patients annually
6. Non-English speaking
7. Unable to access the internet